The question of whether drug abuse results solely from environmental factors, from genetic components or from a combination of both needs to be answered. If both genes and environment are found to influence drug abuse, the relative contribution of each is an important question. to answer these questions, a pharmacogenetic model for drug response is needed. The objective of this project is to establish a pharmacogenetic model for response of mice to pentobarbital. this will be achieved by selection for pentobarbital sleep time response. Divergent selection for pentobarbital sleep times will be performed to form long and short sleep time mouse lines. It is expected that during the first four years of the project, twelve selected generations of mice will be obtained. By that time, the selected mouse lines will be clearly distinct in their sleep time response to pentobarbital. Further selection will continue to differentiate between the lines. These lines will be used to test the effect of selection response to pentobarbital on the pharmacological response to ethanol, morphine, nicotine and amphetamine. changes in the response to these drugs in the different selected lines will provide better understanding of the mechanisms of action of these drugs. These lines will also be used in studying different levels of brain neurotransmitters and in studying drug metabolizing enzymes to detect causes of difference in response to pentobarbital. The selected lines will then be available to researchers nationwide to help expand knowledge of the genetic differences of the pharmacokinetics, pharmacodynamics, and metabolism of barbiturates. Also, one graduate and two undergraduate minority students will be trained in this project. They will gain experience in the field of pharmacogenetics. This should stimulate their interests sufficiently that they will pursue a biomedical research career.